Is ABCF3 p.Lys294Arg (c.881A>G) pathogenic?

ABCF3 p.Lys294Arg (c.881A>G) is classified Uncertain significance in ABCF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-27). AlphaMissense: likely benign (0.0642); Ultra-rare (popmax 0.0201%, eas).

How common is ABCF3 p.Lys294Arg (c.881A>G) in the general population?

ABCF3 p.Lys294Arg (c.881A>G) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

What do computational predictors say about ABCF3 p.Lys294Arg (c.881A>G)?

AlphaMissense predicts likely benign (score 0.0642) — an in-silico prediction, not a clinical call.

ABCF3 p.Lys294Arg

c.881A>G · VCV4142756

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0642 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0642	likely benign
REVEL	0.361	indeterminate
SaProt	LLR -5.19	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 7,487 bp · p 0.0068 · regional, not allelic
Overall
CADD	18.56	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0201% East Asian · 9/44,884 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00062% 10/1,613,994 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,987
European (non-Finnish)	8.48e-05%	1,179,912

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCF3
Protein: p.Lys294Arg
Coding: c.881A>G
MANE Select: NM_018358
Type: single nucleotide variant
Location: chr3:184188805 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.77
Residue 294: the abc transporter 1 domain

Full ABCF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCF3 p.Ala128Ser Uncertain significance ★ ⚠ same type
ABCF3 p.Ala196Val Uncertain significance ★ ⚠ same type
ABCF3 p.Ala280Thr Uncertain significance ★ ⚠ same type
ABCF3 p.Ala293Thr Uncertain significance ★ ⚠ same type
ABCF3 p.Ala303Gly Uncertain significance ★ ⚠ same type
ABCF3 p.Ala312Gly Uncertain significance ★ ⚠ same type
ABCF3 p.Ala312Thr Uncertain significance ★ ⚠ same type
ABCF3 p.Ala391Thr Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abcf3-p-lys294arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown